8-Chloro-3-fluoro-indolo[2,1-b]quinazoline-6,12-dione | 169037-48-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-Chloro-3-fluoro-indolo[2,1-b]quinazoline-6,12-dione
• 英文别名: Indolo[2,1-b]quinazoline-6,12-dione, 8-chloro-3-fluoro-；8-chloro-3-fluoroindolo[2,1-b]quinazoline-6,12-dione
• CAS: 169037-48-3
• 化学式: C₁₅H₆ClFN₂O₂
• 分子量: 300.676
• InChiKey: QUVVHRRCMVEHJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-氟-2H-3,1-苯并噁嗪-2,4-二酮 、 5-氯靛红 在 三乙胺 作用下， 以 甲苯 为溶剂， 以77%的产率得到8-Chloro-3-fluoro-indolo[2,1-b]quinazoline-6,12-dione
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationship Studies of Tryptanthrins As Antitubercular Agents

  摘要：

  The natural product tryptanthrin (la) represents a potential lead for new tuberculosis (TB) drugs since tryptanthrin and its synthetic analogues possess potent in vitro activity against Mycobacterium tuberculosis (Mtb). However, in spite of their in vitro activity, none of these agents have been shown to be efficacious in vivo against animal models of TB. Described herein are syntheses of new tryptanthrin analogues together with a systematic investigation of their in vitro antitubercular activity and ADME properties followed by pharmacokinetic characterization in rodents for the most promising compounds. Those with the best potency and oral bioavailability were progressed to evaluations of efficacy against acute murine TB. The work aimed to prove the concept that this compound class can limit growth of Mtb during infection as well as to establish the SAR for in vitro activity against Mtb and the range of in vitro ADME parameters for this class of natural products. Novel C-11-deoxy (5b) and A-ring-saturated (6) tryptanthrin analogues were discovered that maintained activity against Mtb and showed improved solubility compared to tryptanthrin as well as evidence of oral bioavailability in rodents. However, neither 5b nor 6 demonstrated efficacy against acute murine TB following administration at doses up to 400 mg/kg daily for 4 weeks. Although 5b and 6 failed to inhibit replication or kill Mtb in vivo, they illuminate a path to new structural variations of the tryptanthrin scaffold that may maximize the potential of this class of compounds against TB.

  DOI：

  10.1021/np3007167

文献信息

• Antimalarial and antiproliferative pharmacophore models, novel tryptanthrin compounds having increased solubility, and methods of making and using thereof
  申请人：——

  公开号：US20040033934A1

  公开（公告）日：2004-02-19

  Disclosed herein is a pharmacophore model for antimalarial activity and methods of making and using thereof. The pharmacophore comprises two hydrogen bond acceptor (lipid) functions and two hydrophobic (aromatic) functions. The pharmacophore model was made using a test set of tryptanthrin compounds which exhibit antimalarial activity. Also disclosed are tryptanthrin compounds having greater solubility and bioactivity as compared to prior art tryptanthrin compounds and methods of making and using thereof. Also disclosed are methods of treating malaria in a subject.

  本文揭示了一种抗疟药物活性的药效团模型及其制备和使用方法。该药效团包括两个氢键受体（脂肪）功能和两个疏水（芳香）功能。该药效团模型是使用一组具有抗疟活性的色胺类化合物试验集制备的。还揭示了具有比先前技术的色胺类化合物更高溶解度和生物活性的色胺类化合物及其制备和使用方法。还揭示了治疗受体内疟疾的方法。
• Use of tryptanthrin compounds for immune potentiation
  申请人：Chiron Corporation

  公开号：US20040241192A1

  公开（公告）日：2004-12-02

  The invention provides immunostimulatory compositions and methods of administration thereof. Also provided are methods of administering a tryptanthrin compound in an effective amount to enhance the immune response of a subject to an antigen. Also provided are methods of administering an effective amount of a tryptanthrin to stimulate the immune response in a subject for the treatment of cancer. Further provided are methods of administering a tryptanthrin compounds as an immunotherapeutic in the treatment of infectious diseases.

  该发明提供了免疫刺激性组合物及其给药方法。还提供了一种给予色胺酸酸衍生物有效量的方法，以增强受体对抗原的免疫反应。还提供了一种给予有效量色胺酸酸衍生物的方法，以刺激受体的免疫反应，用于治疗癌症。此外，还提供了一种给予色胺酸酸衍生物作为免疫治疗剂治疗传染病的方法。
• USE OF TRYPTANTHRIN COMPOUNDS FOR IMMUNE POTENTIATION
  申请人：VALIANTE Nicholas M.

  公开号：US20120244182A1

  公开（公告）日：2012-09-27

  The invention provides immunostimulatory compositions and methods of administration thereof. Also provided are methods of administering a tryptanthrin compound in an effective amount to enhance the immune response of a subject to an antigen. Also provided are methods of administering an effective amount of a tryptanthrin to stimulate the immune response in a subject for the treatment of cancer. Further provided are methods of administering a tryptanthrin compounds as an immunotherapeutic in the treatment of infectious diseases.

  本发明提供了免疫刺激组合物及其给药方法。还提供了一种给予吲哚丹宁化合物有效量的方法，以增强受体对抗原的免疫反应。还提供了一种给予有效量的吲哚丹宁化合物的方法，以刺激受体对癌症的免疫反应。此外，还提供了将吲哚丹宁化合物作为免疫治疗剂治疗传染病的方法。
• INDOLO 2,1-b|QUINAZOLE-6,12-DIONE ANTIMALARIAL COMPOUNDS AND METHODS OF TREATING MALARIA THEREWITH
  申请人：Walter Reed Army Institute of Research

  公开号：EP1032574B1

  公开（公告）日：2007-06-13
• EP1594524A4
  申请人：——

  公开号：EP1594524A4

  公开（公告）日：2008-09-03